The CHAIN Program

Forging evolutionary links to underlying mechanisms

Many important principles underlying how protein molecular machines work lie beyond the pale of direct experimental observation. CHAIN analysis is a statistical solution to this problem that follows Mendel’s example: Just as Mendel inferred principles underlying genetic mechanisms from observed patterns of inherited traits, CHAIN analysis seeks to infer principles underlying molecular mechanisms from observed patterns in protein sequences—the cell’s own language for encoding those mechanisms. Sequence patterns that have been conserved for a billion years or more reflect strong selective pressures maintaining mechanistic similarities. Divergent patterns that are conserved in descendent proteins maintaining a particular divergent function likewise reflect mechanistic differences. Thus, non-random patterns of sequence conservation and divergence correspond to conservation and divergence of underlying mechanisms, which we define broadly to include all atomic properties (structural as well as strictly mechanistic) that are required for the function of a protein.

Released in conjunction with a Trends in Biochemical Sciences article describing the CHAIN program (TiBS 32:487-493,2007).